Athena Aktipis (00:04): Have you been zombified by pregnancy or placentas or babies or children? Any of those things? Welcome to the Zombified podcast, your source for fresh brains. I'm your host, Athena Aktipis, psychology professor at ASU and chair of the Zombie Apocalypse Medicine Alliance. Dave Kenrick (00:26): And I'm your cohost, Dave Lundberg-Kenrick, community outreach program manager and brain enthusiast. Athena Aktipis (00:32): Mmm, brains. [Dave agrees] And today, also placentas. Dave Kendrick (00:36): Mmm. They're like the brains of the uterus? Athena Aktipis (00:40): [Laughs] Something like that. [both laugh] Yeah so the placenta is actually, it's an organ that is the same genetically as the baby, like the fetus. It's not like an organ of the mom, genetically, it's an organ of the baby. Dave Kendrick (00:56): Cool. [Athena agrees] So then they take over the mom? Athena Aktipis (01:01): Yeah, exactly. Dave Kenrick (01:02): Interesting. Athena Aktipis (01:04): So, that's what we're going to be talking about today with David Haig, who is a professor at Harvard. He's a biologist who has worked on placentas, pregnancy, and parental investment across lots of different kinds of organisms and how awesomely creepy it sometimes is. Dave Kendrick (01:26): So what, uh, what's your favorite part? What does he talk about? Athena Aktipis (01:30): I think the part where he talks about sharks and shark pregnancy. And I'm not, I'm not going to spoil it by saying what he says about shark pregnancy. I think you should listen and hear for yourself. Dave Kendrick (01:44): Cool! Is there any useful take home advice for either parents or babies or baby sharks? Athena Aktipis (01:54): [Laughs] And mama sharks and papa sharks? [both laugh] Yeah, I think that the big picture is really that yes there is, you know, a lot of-- there are a lot of aligned interests between parents and offspring, but they're not entirely aligned. There's some conflict that's there and it has evolutionary roots and if we understand it better then I think we could actually do a better job of managing that conflict in a way that makes our babies not act like shark babies. Dave Kendrick (02:29): Alright, sounds good. Athena Aktipis (02:32): All right, so let's hear from David Haig. Intro (02:35): [Psychological by LEMI] Athena Aktipis (03:11): Just because, you know, I know you, we know each other. I don't even know-- how long have we known each other? David Haig (03:20): That's a good... it's been a while. When was it? Athena Aktipis (03:21): Well, so, I know we knew each other before you came to Vico, cause- David Haig (03:25): Yeah, no, no, you were invited... I think it was probably, uh, evolutionary medicine-- It was before you went to, uh, before you went to Arizona. Where were you before Arizona? Athena Aktipis (03:42): I was at UCSF. David Haig (03:42): Yeah, no, I saw you- Athena Aktipis (03:44): And before that I was at Kent. David Haig (03:44): I was there where you announced your engagement to Carlo. [Athena agrees] Athena Aktipis (03:49): That's right! You were like sitting at our table when-- [David agrees]. So that, yeah, I remember Carlo was like, "David Haig gave me a kiss on the cheek!" [Laughter] It was like- David Haig (03:59): Oh, I'm a rat bag. Sorry, that's an Australian-- [Laughter] Athena Aktipis (03:59): What does that mean? David Haig (04:06): Rat bag? Oh, sort of a crazy person. Kind of. Athena Aktipis (04:11): Awesome. Well, you're so perfect for this podcast. [David laughs] I've got my crazy hair, you've got your rat bag persona and we'll just, we'll just bring it. [David agrees.] So, um, so we know each other really well, but the people who are with us today listening, they don't know you. David Haig (04:28): Ah. Athena Aktipis (04:28): So maybe you could just in your own words, introduce yourself. David Haig (04:31): I'm a person who prefers no introduction. [laughter] Athena Aktipis (04:35): He needs no introduction, but [laughter] David Haig (04:38): Yes, yes. I'm Australian, as you might be able to detect. Oh, it's hidden beneath the veneer of adolescent pretensions and vaguely British hints to the, uh, to the accent from watching too many, um, BBC period dramas when I was a young man. Athena Aktipis (04:57): Oh, wow. David Haig (04:59): There sort of upstairs downstairs sort of thing. [Athena laughs] No, but I wish I could, I really do, the broad Australian accent, but I can't retain it for the whole of the interview. Athena Aktipis (05:11): I see. [laughs] So you've got your mix of the British-Australian kind of-- David Haig (05:18): Uh, somewhere, mid-Pacific or something, who knows. Athena Aktipis (05:21): Right, right, right, right, right. So, um, but you're a professor. David Haig (05:25): I profess to be a professor, yes. [Athena laughs] Here at, uh, who knows why here at Harvard University in this beautiful office, which the people on the podcast can't see... Athena Aktipis (05:38): Yeah, it's pretty awesome. It's like a long wooden table and beams, long wooden beams and books everywhere. David Haig (05:46): It used to be the malacology collection in the museum. Athena Aktipis (05:50): What's malacology? david (05:51): The study of mollusks. Seashells and things like that, but they've all been put underground and I've been, I'm the specimen now. Athena Aktipis (06:05): Athena laughs] Awesome. David Haig (06:06): Right! Malacology; trivia word for you. Athena Aktipis (06:09): That's right! Yes, malacology. Um, okay, so we're here in your amazing office in the, it's called the Department of Organismal and Evolutionary Biology, right? David Haig (06:19): No, actually Organismic and Evolutionary Biology. Athena Aktipis (06:24): Organismic, I'm sorry, oops. [Laughter] David Haig (06:24): That's okay. Oh, it has "organismal" but some committee came up with "organismic," uh, it once appeared in the Harvard catalog as the Department of "Orgasmic"-- Athena Aktipis (06:37): [Laughs] Oh no, really? David Haig (06:37): It didn't increase our enrollment, [Athena laughs] but I bet there was a time when the Microsoft spellchecker would automatically correct it to "orgasmic." Yes. So it got out there for a while. [Athena laughs] Nothing to do with my study, I much prefer mollusks. Athena Aktipis (06:57): Yeah. Yeah. That reminds me, I had a, um, very, very embarrassing slide once. So, I had someone making figures for me and like, one of the things on the slide should have said "public good," but for some reason they put "pubic good" and I gave a very important talk that had that in it and it was so embarrassing. And like now I just go through and I try to, like, in every of my, you know, old files of my presentations, like I'll find that slide and it keeps creeping up and I'm like, "Delete! Delete!" [laughs] I don't want that to ever happen ever again. So, yeah. David Haig (07:32): [Agrees] But it's out there on the internet, somewhere. Athena Aktipis (07:33): It is! Yeah, yeah. So that is the spellcheck, or just people's errors, and then they propagate. David Haig (07:41): The zombie memes. Athena Aktipis (07:43): That's right! Exactly, yeah. Okay, so we're here at Harvard in your amazing office and you have studied all sorts of really kind of crazy things that happen in biology, things that kind of defy a lot of our intuitions about how organisms work. [David agrees] Yeah. Um, and in particular, I think the thing I'll sort of focus on today, but we don't have to just talk about that, is maternal-fetal conflict. David Haig (08:16): Yeah, pregnancy. Athena Aktipis (08:17): Yeah. So how did you start studying-- how did you get into this sort of question about maternal-fetal conflict? Where did, what was your entry point into it? David Haig (08:29): Well, this is going to be tedious for your audience, but, uh, I did my PhD on, um, parent offspring relations in seed development, um, in plants. Athena Aktipis (08:40): So, so you're saying that plants have babies too? David Haig (08:44): Yes, yeah. They have an embryo attached to the mother that produces, uh, structures that are absorbing nutrients from the mother. You know, come to think of it, we're just rather like plants, really. A baby's a bit like a seed a developing there and uh-- Athena Aktipis (09:04): Okay. So I have to ask, cause you know, when I think about like the evolution of life, I think maybe I'm just very mammal-centric, but I'm like, "Oh, mammals! Like they came up with this idea of parental investment!" But now I realize I'm like, completely wrong. David Haig (09:16): No, yeah not at all-- Athena Aktipis (09:16): That's not really how it works. David Haig (09:17): Yeah. I have a course I called "Vertebrate Viviparity," which was chosen for the alliteration. [Athena laughs] Uh, and it looks at, um, the many origins of life, birth and pregnancy. Uh, it's probably evolved about a hundred times in lizards and snakes. So that's where the action-- Athena Aktipis (09:39): What!? Pregnancy evolved how many-- David Haig (09:40): Yeah, a hundred or-- there's only one in mammals, but if you want to do the origin of, um, live birth and pregnancy, um, lizards and snakes or "squamates," if you want to be, um, sort of logically correct, is where the action is. But my, my favorite, uh, lecture in that course is actually on sharks. So the majority of sharks give live birth and, uh, become pregnant. Uh, and the great white shark is a, is a nice example. Uh, so they have a, it's about a 10 month pregnancy, similar to humans, but they're, uh, the mother just continues to ovulate the whole way during pregnancy and the fetuses sit there and they eat egg breakfasts every day. Athena Aktipis (10:30): What!? David Haig (10:30): And they can eat, you know, hundreds, maybe a thousand eggs during the pregnancy. Um, and that's the way they get-- Athena Aktipis (10:39): That's crazy! [Laughs] David Haig (10:40): [Dave agrees] Now in the sand tiger shark, they don't, uh, they don't just stop at, um, at eating eggs. A practice, there's another word, adelphopagy, "adelpho" is your brother and "phagy" is "to eat." Or to use a more descriptive term, "intra-uterine embryonic cannibalism." And so, um, the fetuses eat each other and only one survives in each uterus and that's the one that's born. Athena Aktipis (11:14): Wow. So, basically there's selection in the womb for cannibalism of siblings and whoever is like the best at eating their siblings...? David Haig (11:24): Presumably, or who gets the start on the other one. [Athena agrees] They start off eating-- Well, you know, if they, if they left their siblings there, they'd be competing for all these eggs being ovulated and so you clean them out first and then you get, uh, you get all the goodies. Athena Aktipis (11:41): So if you're a shark, it's like you start your life, like, in the zombie apocalypse. David Haig (11:45): Well this is, uh, one-- Athena Aktipis (11:45): It's like cannibalism and-- [laughs] David Haig (11:50): This is, this is the, okay another technical term, this is the lamniform sharks. They're the group to which the great white shark and the thresher shark belong. There are other sharks that develop placentas. Um, all of the rays give life birth, but they, um, do uterine lactation. They produce, they produce, you know, nutrient-rich fluids that are secreted into the uterus and the, the embryo is just sitting there and swallowing all that uterine milk. Uh, so they have quite, uh, for sharks and rays, quite quick pregnancies. Athena Aktipis (12:30): Wow. Well, and so it sounds like pregnancy is not all harmony and sweetness [David agrees] and wonderful family feelings. [Athena laughs] David Haig (12:41): [Agrees] It's, it's, this is the theory of parent-offspring conflict. Uh, it's, it's-- my own perception of parent-offspring conflict is that, um, offspring understand it absolutely. They realize that there's not sweetness, light, and harmony in their relationship with the parents whereas parents have the other, um, perception. You know, they feel that everything they're doing is for the best of their, uh, children. [Athena agrees] Uh, natural selection selects for maximizing the number of, um, surviving successful offspring, which is a little bit different from maximizing the survival of any particular, um, offspring. And so-- Athena Aktipis (13:31): So that's kind of where it all starts. That's where parent-offspring conflict starts, is that the survival and wellbeing of one particular offspring is not exactly the same as maximizing the survival and wellbeing of all of your offspring. David Haig (13:45): That's, that's right. Um, it's curious. Uh, people have trouble with parent-offspring conflict because we, we love our children, but, um, they're very okay with sibling rivalry, [Athena agrees] with competition among brothers, brothers and sisters and all parent-offspring conflict is, um, that competition for maternal or paternal care. Um, you know, if you take something from the parent, it's not available for the parent to give to other offspring. And so in my mind, um, they're, they're very, very similar sorts of concepts. [Athena agrees] It's just that we, we tend to portray the parental, particularly the maternal relationship as, as very, uh, it's very simple. [Athena agrees again] So you can think, you know, in the case of, um, a great white shark, probably not all of those eggs are actually fertilized. Some of them are, but you know, it's a way of, um, using one potential offspring to- Athena Aktipis (14:55): To feed another! David Haig (14:55): Yeah, to feed another offspring. [Athena laughs] And also in fact, actually that's one of the copious forms of maternal care is uh, because yolk in, in an egg is the, well, you know, an embryo has all it needs to develop. If you think of a chicken, a chicken in an egg, it's sitting there in the yoke. It's the, that's the perfect food. So if you're wanting to provide more food to, uh, to an offspring, um, feed them eggs! And there are a lot of, uh, there are quite a number of frogs that do that and so rather than put their, um, tadpoles in a stream where there are a lot of things that would like to eat tadpoles, uh, they might put them in a bamboo stump or in, uh, high up in a tree in a little tree hollow somewhere where they're protected from predators but, uh, there's not much to eat there and so, so the mother will come back and will lay eggs periodically to, to feed the tadpoles. Athena Aktipis (15:55): Mmhm, because from the mother's perspective, it's better that the siblings eat each other than that some predator eats them? David Haig (16:00): Well, no-- [Athena laughs] you know, if these, in some cases, they're, um, fertilized eggs, uh, but in other cases, it's just the way of-- Athena Aktipis (16:10): Okay. David Haig (16:10): You know, it's just like lactation, it's a way of providing nutrients. So it's, it's the reuse of, uh, existing structures for a new use. [Athena agrees] And there's a, there's a Taiwanese frog that, that puts it's, um, eggs in bamboo stumps, you know, in broken off bamboo stumps in a little pool of water. And so the tadpoles are all waiting there and when mom comes back to lay an egg, they're like little chicks in the nest. They're all begging there, "feed me, feed me, feed me!" [Athena laughs] So, uh, yeah. Um, you know, if you think about human pregnancy, there's pretty good evidence that probably the majority of all conceptions, um, are lost very early on in, you know, within the first couple of weeks after conception. You know, the embryo implants in the, in the lining of the uterus and when a woman menstruates, if there's an embryo implanted, the embryo is, is flushed out. And so I think there's selection going on there to pick, um, good quality embryos. So there's a sort of a, a testing phase there. Athena Aktipis (17:24): Interesting. Yeah. David Haig (17:24): You know, and this is occurring before you would know there's a pregnancy. [Athena agrees] A more extreme version of that, well, it's a more obvious version of that is in, uh, in quite a lot of marsupials where most of, uh, maternal-- most of the cost of maternal care is occurring after birth, um, suckling offspring, providing milk in the pouch, and at birth, the offspring are really, really tiny... so let's, let's take an example of the Tasmanian Devil, which everybody knows from Bugs Bunny or wherever-- Athena Aktipis (17:59): Speaking of cannibals. [Laughs] David Haig (18:00): Uh, they-- Athena Aktipis (18:00): They at least bite each other's faces. David Haig (18:05): They bite each other's faces. Athena (18:05): I'm not sure if they're actually cannibalistic, but they're, I mean, they're the closest organism that we have to like what a zombie apocalypse would look like. Right? [David agrees] I mean, they're, they're crazy and they're biting each other's faces. So, yeah. David Haig (18:18): Yeah, that's, that's right. [Athena laughs] But, uh, you know, they-- I should have done my research before coming here, [laughter] but I, I think they have, they have four nipples in the pouch, but they, um, they give birth to many more than that offspring, you know, 10 or so and so there's a race and they all race into the pouch to get a nipple. And, um-- Athena Aktipis (18:43): Not all of them make it. David Haig (18:45): Not all of them make it, and actually probably, talking capitalism, you know, the, the extra ones disappear and the most likely possibility is mum then eats the surplus offspring. And in, you know, some of the smaller insectivorous marsupials, uh, mothers actually control the sex of their offspring by selective removal from the pouch. [Athena agrees] So sometimes mothers will eat, eat off the nipple, her, her daughters, and will get a male-biased litter or eat her sons and get a female-biased litter. Athena Aktipis (19:20): So we've got infanticide, we've got cannibalism, we've already like gone super dark in terms of like, what happens, but so let's go now into the darkness that we don't even realize in the human womb. Right? Like so the whole-- David Haig (19:36): Oh, it's pretty dark in there, I can remember. [Athena laughs] Athena Aktipis (19:40): So this, you know, this whole idea of parent-offspring conflict, we were sort of talking about it earlier, that like it comes down to this issue of, like, what is the optimal amount of investment for the mother and that- in each offspring- and what's the optimal amount of investment from each offspring's perspective. And there's some conflict over that, right? Like the optimal- [David agrees] The optimum the mom wants to invest is not as high as the optimum that the offspring would want to extract because mom has multiple offspring, right? And she's trying to- David Haig (20:13): And she's got to care for existing offspring and keep herself healthy and you know, there, there are all sorts of opportunity costs there. So I talked earlier about how, and it's a distinctive human feature, that the human embryo is not actually sitting in the uterus but burrows into the lining of the uterus and it makes contact with maternal blood vessels. [Athena agrees] And so during pregnancy, maternal physiology is coming under joint, um, control because that embryo, this is a very little embryo but it gets larger and larger, is actually secreting lots and lots of hormones into the maternal bloodstream that are taking over maternal physiology to serve its ends. [Athena agrees] And it's mobilizing, um, tap reserves from the mother. So very early on, um, it's, it's just trying to-- so the very, very first hormone that we can talk about is human chorionic gonadotropin, which is what you look for in a home pregnancy test. But essentially what that's doing is it's keeping, um, the maternal ovary pumping out progesterone, which is to stop menstruation. Athena Aktipis (21:28): Pro-gesterone, right? David Haig (21:34): Yeah, it's promoting pregnancy. Athena Aktipis (21:35): Yeah, right. New Speaker (21:35): The maternal ovary in a, in a normal cycle, it stops producing progesterone and that leads to the shedding of the lining of the uterus, that menstruation, once again, that's a primate specific-- It's blocking that, it's stopping that-- Athena Aktipis (21:49): It's the very beginning, it's like hijacking the maternal system so that it can stick around. [David agrees] David Haig (21:55): And there's this strong correlational evidence that those hormones, um, particularly some parts of human chorionic gonadotropin, is also what's responsible for the nausea and vomiting that women experience early in pregnancy. Now, um, there's much debate. Is that just a side effect of this hormone being produced in such large amounts or is it adaptive in some way? Um, the major adaptive hypothesis is that, uh, you know, very early on when the embryo's forming its own organs, uh, it doesn't need a lot of nutrients from the mother, but, um, there are dangers for toxic substances that are in the diet and in what the mother's eating. [Athena agrees] And so one one hypothesis that Paul Sherman has, um, pushed it was Paul's Sherman at Cornell is that, uh, this is you know, putting the mother off of food is in some sense potentially protecting, um, the early embryo from noxious stuff in the maternal diet at a stage where it doesn't need a lot of nutrients to survive. Um, that tends to go away as it depends on mother feeding to supply nutrients to it. Now there are a series of all sorts of other hormones that are going into the maternal bloodstream-- Athena Aktipis (23:24): Yeah, so what are some of those other like mechanisms? Like ways that- David Haig (23:29): Oh for example growth hormone, so you know, all of the growth hormones circulating in the maternal bloodstream at, um, towards the end of pregnancy is coming from the placenta, not from her own body. Athena Aktipis (23:42): Yeah. So maybe, should we talk about the placenta for a minute? [David agrees] Like, what, like what is a placenta? You know, and is it part of the mother's body or a part of the-- I know the answer, but I just want you to say it, yeah. [Laughter] David Haig (23:55): Oh well if you know the answer, you can tell them. I don't need to tell them! [Both laugh] I can sit and relax and uh- Athena Aktipis (24:04): But , yeah, I mean the fact that the placenta-- David Haig (24:05): That the placenta is an organ, but it's a specific feeding organ of the, um, derived from-- well, to give a technical term again, the conceptus, the thing that's conceived. [Athena agrees]. Uh, so it, um, you know, it's a discardable organ that is formed just during the pregnancy to, to be involved in transfer of resources from the mother and also release of wastes into the, uh, into the mother's bloodstream. Now- Athena Aktipis (24:35): Can we kind of think of it as like the organ that is there to like zombify the mom? David Haig (24:41): You can think of it that way, yeah. [Athena laughs] But it's, uh, what we, what we now know is that, so I briefly alluded that the placenta actually invades into maternal tissues. So what it does very, very early on is it breaks into maternal blood vessels, um, bringing blood into the uterus and it modifies those vessels so that they can't constrict and it expands their diameter to increase the flow of blood coming to the, um, to the placenta. Athena Aktipis (25:16): So it's not just hormonally hijacking mom, it's actually like physically it's changing the physiology [David agrees] so that the mom can't help but provide resources for the offspring through the blood. David Haig (25:28): Yeah. And it's also sending off, it's not just hormones it's sending into the maternal bloodstream. We now know that, uh, there are cells coming from the placenta that are circulating in the maternal blood and that they can-- Athena Aktipis (25:44): We're going to talk to Amy! [Laughter] We're going to talk to Amy in a few episodes! David Haig (25:49): Oh, you're going to talk to Amy? Oh then I won't steal her thunder, on this but, basically, um, placentally derived cells can get practically anywhere in the mother's body and who knows what they're doing? Athena Aktipis (26:00): Probably zombifying! [Laughs] David Haig (26:01): Zombifying, yeah, um you can bet that they're, um, changing maternal behavior in ways that are good for that, that, uh, fetus. [Athena agrees] And we know that they just hang around for a long time. Athena Aktipis (26:20): And express genes, and all sorts of stuff. David Haig (26:20): Yeah, we know that, you know, once a woman's been, uh, pregnant, as I believe you have been at least, well-- Athena Aktipis (26:27): Yeah, yep. At least three times. [laughs] David Haig (26:27): At least three times! Yeah, so. Uh, probably- Athena Aktipis (26:30): I've got a lot of cells. [Dave agrees] David Haig (26:31): You've got cells from Vaughn, Monte and-- Athena Aktipis (26:41): Ivana. David Haig (26:41): Ivana! Athena Aktipis (26:42): Amazing! David Haig (26:42): [Athena laughs]They're sitting your body at this moment just helping you out at this stage. Athena Aktipis (26:48): Yeah, I'm sure they're all completely helpful. Probably. [laughter] David Haig (26:53): Well, you know, I think they probably should be at this stage- Athena Aktipis (26:55): At this point. David Haig (26:55): You know, because, because Monte's cells sitting in you, the only reason that they would be-- Athena Aktipis (27:00): They've got mostly aligned interests and keeping me alive right now? David Haig (27:03): Yeah, yeah. You're, you're good value. [Athena laughs] And it's, I find it hard to imagine that Monte's cells in you could be modifying your behavior in ways to be good to Monte and not to Ivana and, and to, to Vaughn. [Athena agrees] You know, they, they don't have a neural system and sentry system, so they've gotta be doing- Athena Aktipis (27:27): Yeah, or, or they did that manipulation in the immediate, like postpartum phase and like manipulated the bonding systems. [David agrees] But now we're just wildly speculating, like completely wildly speculating, so-- David Haig (27:44): How personal do you want to get? [Both laugh] Maybe not too personal, but uh, Vaugn's the young one? Athena Aktipis (27:51): The little one, yeah. David Haig (27:51): Yeah, yeah, yeah. You know, and so he has a, he has a different father from the older two and-- Athena Aktipis (27:58): That's right, yeah. David Haig (27:58): And so I can imagine some fairly intense competition there between, uh, his paternal, paternal genes and those of his older half siblings, you know? [Athena agrees] And so that's another part of my, uh, research is on the internal conflicts within the, uh, within the individual, um, between genes of maternal and paternal origin. Athena Aktipis (28:21): So it's like a microchimerism zombie apocalypse happening inside me all the time, is what you're saying. David Haig (28:27): And within individual cells, yeah. Athena Aktipis (28:30): Oh, and even in the cells, right. Yeah. David Haig (28:33): You can think about the, you know, I've, I've thought about this actually with, with partner change, you know, one of the, one of the limits on sibling rivalry is the genetic relatedness among the children. If we're talking about full siblings, or as I prefer to say, double half-siblings, [Athena laughs] they have the same mother and father and on average, um, if you pick a gene in one of them, it's got a 50% chance of having a copy in the other and that, um, so you can't be too nasty to your, to your, um, siblings because, uh, in a genetic sense it can be doing in your relatives. But if you think about, uh, a maternal half-sibling, you know, so you'll have a, have a partner change. Um, as far as the, uh, existing maternally derived genes, the genes that you get from you [referring to Athena], uh, the, the youngest sibling is just another relative probability of half. But from the point view of paternally derived genes from your former, former husband, any other offspring that you have is just resources-- that's a non relative resource-- Athena Aktipis (29:51): Yeah. Unless there's like some other ways that their fitness is interdependent or their well-being. So like the way I solve this in my house is, you know, they're kids and they love their screen time and so everyone gets the same amount of screen time every week. And if anyone is misbehaving, they all lose screen time, so-- David Haig (30:09): This is zombie mother! [Both laugh] Are we allowed to talk about having kids? [Athena agrees] Athena Aktipis (30:20): You have kids too. David Haig (30:20): Yeah, I have kids too. Actually like you, uh, I have three children, one of whom has a, has a different, uh, in this case mother from the other two. And so these, these conflicts can sort of get out there. [Athena agrees] Yeah. Oh, back to pregnancy. Athena Aktipis (30:42): Yes, yes. And I definitely want us to have a chance to talk a little, a little bit about preeclampsia, cause I think that is fascinating and crazy and really just like ties into, you know, well what happens when this conflict escalates? David Haig (31:01): Gets out of control. Athena Aktipis (31:01): Yeah, yeah, yeah. So maybe, you know, we were, so we were talking about the placenta, right? And like how it sets up this resource flow situation. Um, so what, what is it that happens in late pregnancy that can lead to preeclampsia and how does it relate to this? David Haig (31:25): So let's uh, uh, what's it, what's in a name? So "eclampsia," and I think it comes from the, um, Greek word for lightning or something like that. Uh, this, uh, so "eclampsia" was, uh, a major complication of pregnancy that was recognized, uh, from, from ancient times. So this, a woman at the time of delivery, um, would, um, undergo convulsions and fits. Um, you know, there was something going wrong in her brain. And so that was called "eclampsia" and it became recognized- Athena Aktipis (32:08): And when did this happen? After birth or during? David Haig (32:10): Oh, so eclampsia is classically immediately after birth, but then it became recognized that most women who experienced, um, eclampsia, um, there were all sorts of other problems in their physiology that were existing in the late stages of pregnancy. Um, the way that this was diagnosed was they developed high blood pressure during pregnancy. Um, they also had the appearance of protein started appearing in their urine. So the way eclampsia-- and so this syndrome was called preeclampsia, which occurred before eclampsia. So, uh, so, eclampsia is really quite rare, but preeclampsia, um, you know, can affect perhaps, you know, five to 10% of women develop high blood pressure and the appearance of protein in the urine towards the end of a pregnancy. The appearance of protein in the urine is just evidence of generalized vascular damage in the mother. So the lining of the maternal blood vessels is becoming, um, damaged because of factors being released by the placenta into the maternal circulation and one place they've been damaged is in the kidneys so the kidneys are no longer being an effective, um, filter. And so you start having blood proteins leaking out into the urine and so that's how it's diagnosed. But as we've come to understand preeclampsia better, it's, it's evident that that vascular damage in the mother is occurring throughout the maternal system. And, um, preeclampsia is a major source of maternal morbidity. Pretty well any maternal organ can fail, you can have cerebral brain effects as in eclampsia, you can have kidney failure, you can have liver failure, heart failure, whatever. Athena Aktipis (34:15): And this is happening because of disruptions to the blood flow and blood pressure. David Haig (34:21): Yeah and what I think is happening is that, uh, there are placental factors being released into the mother that are actually causing vascular damage, which causes maternal blood vessels to constrict and that has the effect of channeling more maternal blood to the placenta so that, um, you know, the maternal blood supply during pregnancy, blood is being pumped into the body, some of it's flowing through the placenta and the other's going to the other maternal tissues. Um, it's a sort of high risk strategy of the fetus to increase its nutrient supply by causing damage in the mother's vasculature that those vessels constrict because of the damage and that forces more blood towards the placenta. Athena Aktipis (35:11): It's like a super, super high stakes temper tantrum. David Haig (35:14): Yes. [Both laugh] Actually that's the perfect analogy. I'll, I'll, I'll use it. [Athena laughs] Temper tantrum would be about right. Yeah. And like a temper tantrum, you know, I need something and I need it now. Athena Aktipis (35:31): And at all costs. David Haig (35:31): And perhaps not at all costs, but you know, I feel, okay, let's talk about pregnancy. [Athena agrees] Just a little, you know, uh, you normally go to the doctor when something's wrong, um, and your heart keeps pumping year after year and your kidneys and all of those things work really well year after year after year and you only rarely go to the doctor. And the one exception is pregnancy. You know, and pregnancy is central to reproduction. But if you're pregnant, uh, you start preparing for the worst, you start going to obstetricians or whatever. We now do births in hospital just in case something could go wrong. And why is that? You know, if producing a baby is so central to reproductive fitness, why doesn't pregnancy work much more efficiently? [Athena agrees] Athena Aktipis (36:32): Why does it hurt so damn much? [laughter] David Haig (36:34): Why does it hurt so--and the reason is parent-offspring conflict. But you know, those other organ systems are working within a genetically homogenous body and so they all work together to enhance your fitness. The problem in pregnancy is you've got this interaction between relatives and relatives have some genes in common, some common interests, but some genes different, some difference and we have this conflict. The fetus is attempting to get a little bit more from mother that's restrained by the mother. But the consequence of this is that there is a breakdown of communication and the feedback controls between um, the mother and embryo. And so the, the physiology of pregnancy I think is inherently unstable because of this inability to, to send, um, messages backwards and forwards between mother and fetus just because-- Athena Aktipis (37:33): It's just, sort of, an incentive to cheat, basically. David Haig (37:37): To deceive, to send misleading, um, you know, the, the mother, if there were a way that the mother could signal to the fetus "just lay off your demands now, um, I really need to be doing something else," mothers will be selected to send that in situations when the fetus could do with just a little bit extra and the fetus will be selected to discount maternal signals and say you have a general breakdown of communication. And so the reason why I think things go wrong so often in pregnancy is because of this breakdown of evolutionary, um, evolutionary trust. Athena Aktipis (38:23): That's really interesting. So basically if we could all just communicate better then, and trust each other, that the information that we're getting is actually reliable then... David Haig (38:35): Well, you know- Athena Aktipis (38:35): There wouldn't be as much of a problem. David Haig (38:39): There wouldn't be. Now you can, you can find nice examples where you have live birth and you have no genetic difference. Uh, so a nice example of that are aphids, those little insects that grow on plants. So, um, they're parthenogenetic, um, and the mother gives live birth and in fact, what you can find within, within an aphid you can find within the female embryos sitting with mothers in their ovaries, they're already forming their female offspring and it's like Russian dolls. You can find embryos within embryos within embryos. And as far as I know, you don't have these complex placental structures developed there because these are, uh, you know, genetically identical. Interestingly, when an aphid becomes sexual, so it's going to produce an offspring that's genetically different from its mother, then it produces an egg. It gets them out of the body. Athena Aktipis (39:39): Oh. David Haig (39:39): And so the sexual offspring develop out of eggs and it's only when they're reproducing asexually that they- Athena Aktipis (39:45): --that they're willing to do it inside, right? David Haig (39:45): Yeah, it seems a sensible arrangement. Athena Aktipis (39:50): Yeah. Yeah. So, um, maybe we could talk just a little bit about the sort of maternal-paternal conflict, cause we've sort of been talking about maternal-fetal conflict but really, you know, underlying that the reason that there is maternal-fetal conflict is because there are paternal genes that are making up half of that fetus. Right? David Haig (40:11): Yeah. Yeah. Athena Aktipis (40:13): So in a way- David Haig (40:15): So this is how I got into pregnancy actually in the, so going back to the-- Athena Aktipis (40:19): The question originally, yes. David Haig (40:19): Before I got distracted from talking about seed development and so I, I was interested in seed development and the different roles of maternal and paternal genes within the developing seed and the base, because, um, a mother plant will often be having seeds with many different fathers. Um, the theories seem to predict to me that uh, genes of paternal origin would be selected to demand more from mothers because they were competing with alternative fathers' genes. Athena Aktipis (40:57): Plants are, like, super promiscuous is what you're saying? David Haig (40:59): Uh, sometimes. Yeah. [Athena laughs] It depends on plants. There are, uh, there, there are some, some plants who, um, Evangelical Christian-- [Athena laughs] well, no, let's not go there because I've known of Evangelical Christians who are super promiscuous, but that's a different, a different issue. But, um, you know, they have model, um, it's the mothers providing the nutrients in the plant, [Athena agrees] but it's been, there's competition among different paternal, um, genes. And so, uh, this I think accounts for a phenomenon that gets called genetic imprinting, which is genes of different, uh, maternal and paternal genes doing different things within the embryo and sometimes in conflict with each other. Athena Aktipis (41:46): Right. So they sort of, in a way "know", I'm putting scare quotes, if they came from the mother or the father because there's different methylation-- David Haig (41:59): They're marked in some way. Athena Aktipis (41:59): Yeah, they have, it's like there's little tags on them. Yeah. David Haig (42:03): Little tags that say "I come from a mom or dad." [Athena agrees] But it's gotta be a tag because the genes I get from my mom, uh, my children are getting from their, their dads. So, even though that gene had a maternal tag in me, it's got to get a paternal tag in my-- Athena Aktipis (42:20): And then kind of depending on whether the tag from mom or dad is there, the genes will get expressed differently. So they'll be like more exploitative of the mom or less. Right. That's the basic idea. David Haig (42:30): You know, like, so they're, there are rare human embryos that are triploid that get, um, two sets of genes from one parent and only one from the other parent. And they come in two different kinds. There are digynic triploids who get two sets of genes from mom and one from dad, and they have a really small placenta, whereas there are diandric triploids who get two sets of genes from dad and one from mom and they have a large placenta. And so this is some evidence that in placental development, uh, genes, genes that the placenta gets from its mother tend to restrain placental growth whereas genes it gets from its father tend to enhance placental growth. Now there's uh, a peculiar kind of pregnancy, which for historical reasons is called a hydatidiform mole, okay this is not a little burrowing creature, it's from mole as in molecule, as a, as a mass. But, uh, essentially a woman becomes pregnant, she starts to grow large rapidly. Now with ultrasound, all that's sitting in the uterus is a massively proliferating placenta-- Athena Aktipis (43:50): Wow, really. David Haig (43:50): It's pumping out lots and lots of these hormones into the mother. She can have severe nausea, all of these symptoms, and those conceptuses turn out to have no genes from the mother except for their mitochondria. Athena Aktipis (44:05): What! David Haig (44:05): There's a fertilized egg, it's been fertilized by two sperm. Somehow the, um, somehow the maternal chromosomes have been eliminated. So you're just looking at the effects of paternal chromosomes. Athena Aktipis (44:20): Wow. David Haig (44:20): And so what you've got is a massively proliferating placenta and they have a very high frequency after the so-called model pregnancies, of what is called choriocarcinoma, which is a really, really nasty cancer. And it's unusual cancer. This is zombie stuff because it's not from the mother's own body. It's derived from the offspring, the placental tissues, and they become cancerous and they're highly invasive and invading your maternal tissues. And before, um, modern chemotherapy and this was essentially a death sentence for, for a woman, uh, you know, 98% mortality within, within five years. It turns out it's quite a treatable cancer because the cancer cells give themselves away because they're, um, they're placental cells and they're producing those pregnancy hormones. And so they allow you to detect whether you've got rid of all of the, all of the cells. Also, fortunately, uh, placental cells turned out to be quite sensitive to some chemotherapeutic reagents so this was a former universally fatal cancer, which now most women who get it, uh, survive. But it's an example. It's, it's, it's showing very clearly that, uh, paternally derived genes coming from the father really, really promoting [Athena agrees] invasion of the maternal tissues. Athena Aktipis (45:53): So it sort of answers the question of like, if two males actually wanted to have an offspring that was just, you know, had no maternally imprinted genes in it, it would just be a giant placenta, basically. David Haig (46:09): That's right. Yeah. [Athena laughs] Sorry, sorry to the same sex male couples out there, [Athena agrees] but there are a few, few problems out there. We know of, um, you can experimentally produce embryos that only have maternal genes, um, and they actually produce most tissues in the embryo. But what they don't produce is the, uh, placenta. Athena Aktipis (46:35): Is this, like, done in mouse models and stuff? David Haig (46:39): It can be done in mouse models, but the, uh, uh, the, the natural pathological example of it, it's what are called ovarian teratomas. So these affect women, they're when, uh, an oocyte, an egg starts to develop without fertilization, so it doesn't have any paternally derived genes. And these are, they're called teratomas. "Teratos" is the Greek for "monster," they produce all the tissues in embryo, they produce teeth and they can produce hairs developing in the ovary [Athena agrees]. So they're pretty ugly looking things. But fortunately they're not, um, invasive because they don't produce, uh, trophoblastic, that's placental, tissues. And so, they are a benign tumor in that sense. They're not a metastatic invasive tumor. And so they're, they're a hint of what happens if you only have maternal genes. Um, they can produce most of the tissues of the body, but they can't, can't produce the feeding structure of the placenta. Athena Aktipis (47:45): Two totally different kinds of monsters basically. David Haig (47:49): Yeah. [Athena agrees]. So we've, we've talked of many zombies here so far. Athena Aktipis (47:52): Yeah. All right, well, so very last question then. So if you take maternal-fetal conflict and the, the mechanisms, you know, that underlie the sort of zombification of like, you know, the fetus hijacking the maternal systems. So the question is, what is the zombie apocalypse of this kind of zombification of fetuses or offspring in general, hijacking their parents to invest in them? Like what does that look like? Is that a good world? Is that a bad world? What happens if we take it to the extreme? David Haig (48:36): I've never watched a zombie movie in my life, so I'm really uninformed about a zombie apocalypses. I, I, I hear that it's a genre out there. [Athena agrees] You know, the- Athena Aktipis (48:50): Like, what's the extreme? David Haig (48:52): We have evolved to successfully produce offspring [Athena agrees] and uh, and offspring survival depends upon having, in humans, healthy, uh, parents all in all. So it works pretty well most of the- [Athena agrees]. You know, I can, uh, I, I could give you an example, you know, of, um, there's a little, a little beetle larvae called micromalthus, perfect name. And they're, you know, the male offspring actually, the description in the paper I read was after he hatches out, he sticks his mouth, he sticks his head into his mother's genital orifice and eats her. And so, you know, there's a situation where the mother is consumed by her offspring soon after birth. So that would be the zombie apocalypse taking over. Athena Aktipis (49:47): I see. So it's like, it's not just like, you know, more health issues during pregnancy and all of that. It's basically like offspring eating their parents. David Haig (49:59): And also that-- Athena Aktipis (49:59): That's what a comparative sort of logical approach would tell us, is that's the zombie apocalypse. David Haig (50:03): She can actually- Yeah, yeah, yeah. She, she generally, you know, and actually it's appropriate that micromalthus, the mother, who is just a beetle grub, she never actually matures, produces lots of daughters asexually because you don't want to reproduce many sons because once you produce that son, he's going to, um- [Athena laughs] he's going to consume you. So, yeah, female-biased sex ratios are good for a micromalthus. Athena Aktipis (50:31): Okay. So in the sort of zombie apocalypse of-- David Haig (50:34): You could be, yeah-- Athena Aktipis (50:34): You know, oh yeah, we'll have some sort of a bias sex ratio. Potentially. [David agrees]. David Haig (50:40): Yeah, it could you know if, um, if offspring ate their parents, we'd soon run out of parents. [Athena agrees] Uh, you know, because it takes two parents to produce one offspring and it's the path to extinction. And it's possible that there are species that we don't know about that have succumbed to the zombie apocalypse and they're just not here now. Yes. Athena Aktipis (51:05): Ooh, children be nice to your parents, otherwise you might go extinct. Right? [David agrees] Yeah? [laughter] David Haig (51:14): Thank you, Athena. Athena Aktipis (51:14): Thank you so much for being here with us today. Outro (51:20): [Psychological by Lemi] Athena Aktipis (52:34): Zombified is a production of Arizona State University and the Zombie Apocalypse Medicine Alliance. Thank you to the Department of Psychology, the Interdisciplinary Cooperation Initiative and the President's Office at ASU. Also a big thanks to the Lincoln Center for Applied Ethics also at ASU. Thank you to all of the brains that help make this podcast to Tal Rom who does our sound, Neil Smith, our illustrator, Lemi, the creator of the song Psychological and a big thanks to our Z-team at ASU, our undergrad zombie apocalypse zombified team. You can follow us and support us by going on Twitter and Instagram. We are zombifiedpod on Facebook. We are Zombified podcast and our website is zombified.org. You can support us on Patreon. We are totally educational and we have no ads so we rely on support from our listeners and if you can afford a dollar a month or maybe even five, we would be very appreciative. You can also support us by buying merchandise, t-shirts, stickers, you can find them all on our website, zombified.org. And don't forget there's another super easy way for you to support us, go and review us, give us an awesome review. Or if you actually don't want to give us an awesome review, just tell us what you think. And you can do that on Apple podcasts where a lot of people will get the chance to see it. Athena Aktipis (54:10): So, as I do at the end of every episode, I want to share some of my brains, and this time I'm going to talk a little bit about a connection to some work that I'm doing with a graduate student of mine. So when David talks about theories of pregnancy cravings, um, he made some references to a old theory and a theory that has been around for a long time that aversions in pregnancy have to do with mothers avoiding toxins in, um, vegetables and things like that. And so I just wanted to offer some, uh, newer thoughts on this that actually dovetail with maternal-fetal conflict as well as the pregnancy cravings issue so I think it's super appropriate for this episode. All right, so here goes. What we know in terms of the evidence? Um, it's clear that the, the previous theories about pregnancy cravings and aversions don't really hold up. There's no solid evidence for the hypothesis that nausea is about avoiding plant toxins. In fact, meat, um, and non-alcoholic beverages like coffees and teas and stuff were found to be the most aversive in the studies that have been done. Um, and fruits and sweets were the foods that were most craved and there isn't really a good existing explanation for why these patterns are in place. Now my graduate student, Jessica Ayers, and I are actually looking at food choice and pregnancy because we think that maternal-fetal conflict might underlie some aspects of it. So here is the idea: maybe cravings for things like fruit and sweets are actually a manifestation of the fetus sort of trying to get the mother to consume food that provide quick and easy sources of sugar for the fetus while the fetus extracts limiting nutrients like calcium from the maternal body. And it turns out that fetuses actually have access to all sorts of, um, the sort of machinery of how hunger and satiety work so the mechanisms are there that it's possible. So, but right now we don't know for sure, we're in the process of collecting data, so stay tuned. I mean, right now we have some interesting preliminary results actually that suggest that both cravings and aversions to foods that we call fetal favoring foods like sweets, um, that those are associated with pregnancy complications like high blood pressure and preeclampsia. And we know that those pregnancy complications stem from maternal- fetal conflict, as we talked about with David Haig in this episode, and a lot of his work has, um, really illuminated that there are pregnancy complications that result from maternal-fetal conflict. So, stay tuned and thank you for listening to Zombified, your source for fresh brains. Outro (57:41): [Psychological by LEMI]